A Biomimetic Nanoparticle to "Lure and Kill" Phospholipase A2. Issue 26 (15th April 2020)

• Record Type: Journal Article
• Authors: Zhang, Qiangzhe; Fang, Ronnie H.; Gao, Weiwei; Zhang, Liangfang
• Is Part Of: Angewandte Chemie international edition. Volume 59:Issue 26(2020)
• Page Start: 10461
• Page End: 10465
• Publication Date: 2020-04-15
• Subjects: attractant -- cell membrane -- enzyme inhibition -- inhibitor -- phospholipase A2; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202002782
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Inhibition of phospholipase A2 (PLA2) has long been considered for treating various diseases associated with an elevated PLA2 activity. However, safe and effective PLA2 inhibitors remain unavailable. Herein, we report a biomimetic nanoparticle design that enables a "lure and kill" mechanism designed for PLA2 inhibition (denoted "L&K‐NP"). The L&K‐NPs are made of polymeric cores wrapped with modified red blood cell membrane with two inserted key components: melittin and oleyloxyethyl phosphorylcholine (OOPC). Melittin acts as a PLA2 attractant that works together with the membrane lipids to "lure" in‐coming PLA2 for attack. Meanwhile, OOPC acts as inhibitor that "kills" PLA2 upon enzymatic attack. Both compounds are integrated into the L&K‐NP structure, which voids toxicity associated with free molecules. In the study, L&K‐NPs effectively inhibit PLA2‐induced hemolysis. In mice administered with a lethal dose of venomous PLA2, L&K‐NPs also inhibit hemolysis and confer a significant survival benefit. Furthermore, L&K‐NPs show no obvious toxicity in mice. and the design provides a platform technology for a safe and effective anti‐PLA2 approach. Abstract : Modified red blood cell membrane is used to fabricate a cell‐like nanoparticle for safe and effective inhibition of phospholipase A2 (PLA2) based on a "lure and kill" working mechanism. The resulting nanoparticle can attract the PLA2 enzyme and subsequently inhibit its bioactivity. As a result, the nanoparticle can effectively inhibit PLA2‐induced hemolysis and protect animals from PLA2‐induced lethality.